This is an investigation to test the possibility that Epstein-Barr virus (EBV) plays a role in the induction of rheumatoid arthritis and of the autoantibodies that characterize the disease. We plan to expand upon the observations that EBV infection of B cells in vitro promotes the production in the B cells of both an antigen (RANA) to which a high proportion of patients with rheumatoid arthritis produce a precipitating antibody (RAP) and an autoantibody (rheumatoid factor) that has long been associated with the disease. A search will be made for evidence by hybridization of EBV genomes in joint tissues and by immunofluorescence for EBV nuclear antigen (EBNA). An understanding of the cellular control mechanisms allowing rheumatoid factor production will be made with in vitro culture techniques using separated and recombined T and B cell populations from diseased and normal persons, assessing rheumatoid factor and total Ig production by radioimmunoassays of supernatants. An assessment of the relative quantities of EBV antigens and antibodies, RANA and RAP, and rheumatoid factors in immune complexes isolated from serum and joint fluids of patients will give some estimate of the relative importance of each of these immune complex systems in the pathogenesis of the disease.